Abstract
Normal pregnancy is a state of hypercoagulability with diminishing fibrinolytic activity, which is mainly caused by an increase of plasminogen activator inhibitor type 1 (PAI-1). PAI-1 is the main inhibitor of plasminogen activators, including tissue-type plasminogen activator (tPA) and urokinase-type plasminogen activator (uPA). In human placentas, PAI-1 is expressed in extravillous interstitial trophoblasts and vascular trophoblasts. During implantation and placentation, PAI-1 is responsible for inhibiting extra cellular matrix (ECM) degradation, thereby causing an inhibition of trophoblasts invasion. In the present study, we have reviewed the literature of various reproductive diseases where PAI-1 plays a role. PAI-1 levels are increased in patients with recurrent pregnancy losses (RPL), preeclampsia, intrauterine growth restriction (IUGR), gestational diabetes mellitus (GDM) in the previous pregnancy, endometriosis and polycystic ovary syndrome (PCOS). In general, an increased expression of PAI-1 in the blood is associated with an increased risk for infertility and a worse pregnancy outcome. GDM and PCOS are related to the genetic role of the 4G/5G polymorphism of PAI-1. This review provides an overview of the current knowledge of the role of PAI-1 in reproductive diseases. PAI-1 represents a promising monitoring biomarker for reproductive diseases and may be a treatment target in the near future.
Highlights
The fibrinolytic system plays a role in several physiological and pathophysiological processes, such as hemostatic balance, tissue remodeling, tumor invasion, angiogenesis and reproduction [1]
plasminogen activator inhibitor type 1 (PAI-1) levels are increased in patients with recurrent pregnancy losses (RPL), preeclampsia, intrauterine growth restriction (IUGR), gestational diabetes mellitus (GDM) in the previous pregnancy, endometriosis and polycystic ovary syndrome (PCOS)
We focus on the complex roles of PAI-1 in normal placentation and reproductive diseases, including recurrent pregnancy losses, preeclampsia, intrauterine growth restriction, endometriosis and polycystic ovary syndrome
Summary
The fibrinolytic system plays a role in several physiological and pathophysiological processes, such as hemostatic balance, tissue remodeling, tumor invasion, angiogenesis and reproduction [1]. UPA plays an important role in a variety of physiological and pathological processes including tissue destruction, inflammatory reactions and invasion of trophoblasts [14] and cancer cells [15] Both uPA and tPA consist of a single-chain form and a two-chain form [4,16]. EVT can degrade extracellular matrix (ECM) to promote cell migration to the maternal side [33] This process is precisely controlled by many factors expressed by maternal cells and trophoblasts (Figure 2) [33]. The limitation of EVT invasion is due to reduced ECM degradation (Figure 2), which requires the balance of promoting and restraining factors, such as metalloproteinases (MMPs) and tissue inhibitors of MMPs (TIMPs), uPA and PAI-1 [40]. PAI-1 inhibiting fibrinolysis and fibrin accumulation are believed to be the principle reasons for RPL, but the understanding of the mechanism of PAI-1 in RPL still has to be further analyzed
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